Abstract
Aims/hypothesisWe aimed to examine the association between midlife type 2 diabetes mellitus and cerebrovascular disease (CBD) in late life, and further to explore whether genetic and early-life familial environmental factors (such as shared childhood socioeconomic status and adolescent environment) play a role in this association.MethodsIn this prospective nested case−control study based on the Swedish Twin Registry, 33,086 twin individuals who were born in 1958 or earlier and were CBD-free before the age of 60 were included. Midlife (40–59 years) type 2 diabetes was ascertained from self-report, the National Patient Registry (NPR) and glucose-lowering medication use. CBD diagnosis (cerebral infarction, occlusion of cerebral arteries, subarachnoid haemorrhage, intracerebral haemorrhage and unspecified CBD) and onset age were identified from the NPR. Late-life CBD was defined as CBD onset age ≥60 years. Generalised estimating equation (GEE) models were used to analyse unmatched case−control data (adjusted for the clustering of twins within a pair). Conditional logistic regression was used in co-twin matched case−control analyses in CBD-discordant twin pairs.ResultsOf all the participants, 1248 (3.8%) had midlife type 2 diabetes and 3121 (9.4%) had CBD in late life. In GEE models adjusted for age, sex, education, BMI, smoking, alcohol consumption, marital status, hypertension and heart disease, the ORs (95% CIs) of type 2 diabetes were 1.29 (1.03, 1.61) for cerebral infarction, 2.03 (1.20, 3.44) for occlusion of cerebral arteries, 0.52 (0.12, 2.21) for subarachnoid haemorrhage and 0.78 (0.45, 1.36) for intracerebral haemorrhage. In multi-adjusted conditional logistic regression, the OR of the type 2 diabetes–cerebral infarction association was 0.96 (0.51, 1.80). The differences in ORs from the GEE and co-twin control analyses were not statistically significant (p = 0.780).Conclusions/interpretationMidlife type 2 diabetes is significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life. Genetic and early-life familial environmental factors do not appear to account for the type 2 diabetes–cerebral infarction association, but further clarification is needed.
Highlights
Worldwide, cerebrovascular disease (CBD) and type 2 diabetes mellitus are common disorders that are among the top ten leading causes of death, killing approximately eight million people in 2016 [1]
Statistical analyses The characteristics of the study population by midlife type 2 diabetes or CBD were compared using χ2 tests for categorical variables, unpaired Student’s t test for continuous variables with normal distribution, and Mann– Whitney U test for continuous variables with non-normal distribution
A Adjusted for age, sex and education b Adjusted for age, sex, education, BMI, smoking, alcohol consumption and marital status c adjusted for hypertension and heart disease covariates, and the results were not significantly altered (ESM Table 2). In this large-scale, nationwide, population-based study of Swedish twins, we found that midlife type 2 diabetes was significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life
Summary
Cerebrovascular disease (CBD) and type 2 diabetes mellitus are common disorders that are among the top ten leading causes of death, killing approximately eight million people in 2016 [1]. In a collaborative meta-analysis of 102 prospective studies including 698,782 participants, the adjusted HR was 2.27 (CI 1.95, 2.65) for ischaemic stroke in people with vs those without type 2 diabetes [9]. Type 2 diabetes may cause atherosclerotic changes in the cerebral arteries, and lead to ischaemic stroke [10]. Several studies have examined the association between type 2 diabetes and haemorrhagic CBD, but with inconsistent results [3, 5, 8, 9, 11,12,13,14,15,16,17,18,19]. No studies have focused on the association between midlife type 2 diabetes and CBD in late life
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